Cengiz Korkmaz

Acute phase response in familial Mediterranean fever

Objective: To test the hypothesis that not all acute phase reactants respond in the same way during attacks of familial Mediterranean fever (FMF) and that there is a subclinical acute phase response (APR) in a proportion of patients during the interval between attacks. Methods: Blood and urine samples were obtained from 49 patients with FMF during an attack and the attack-free period that followed, to test for erythrocyte sedimentation rate, C reactive protein (CRP), fibrinogen, white blood cell count, platelet count, factor VIII related antigen, haptoglobin, protein electrophoresis, ferritin, proteinuria, and haematuria. Control groups comprised 29 patients with juvenile idiopathic arthritis, 10 patients with various infectious diseases, and 19 healthy subjects. Results: A marked APR was seen during the FMF attacks which was comparable with that obtained in the diseased control groups. CRP was the only acute phase protein that was raised during all attacks. Neither thrombocytosis nor an increase in ferritin levels (except one) was noted in any attack. Serum albumin levels remained unchanged. In two thirds of the patients with FMF a continuing APR was seen in between the attacks. Conclusion: Platelet, ferritin, and albumin responses are not part of the significant APR seen during short lived attacks of FMF, and inflammation continues in about two thirds of the patients during an attack-free period.

Apremilast for Behçet’s Syndrome — A Phase 2, Placebo-Controlled Study

BACKGROUND Oral ulcers, the hallmark of Behçets syndrome, can be resistant to conventional treatment; therefore, alternative agents are needed. Apremilast is an oral phosphodiesterase-4 inhibitor that modulates several inflammatory pathways. METHODS We conducted a phase 2, multicenter, placebo-controlled study in which 111 patients with Behçets syndrome who had two or more oral ulcers were randomly assigned to receive 30 mg of apremilast twice daily or placebo for 12 weeks. This regimen was followed by a 12-week extension phase in which the placebo group was switched to apremilast and a 28-day post-treatment observational follow-up phase. The patients and clinicians were unaware of the study assignments throughout the trial. The primary end point was the number of oral ulcers at week 12. Secondary outcomes included pain from these ulcers (measured on a 100-mm visual-analogue scale, with higher scores indicating worse pain), the number of genital ulcers, overall disease activity, and quality of life. RESULTS The mean (±SD) number of oral ulcers per patient at week 12 was significantly lower in the apremilast group than in the placebo group (0.5±1.0 vs. 2.1±2.6) (P<0.001). The mean decline in pain from oral ulcers from baseline to week 12 was greater with apremilast than with placebo (-44.7±24.3 mm vs. -16.0±32.5 mm) (P<0.001). Nausea, vomiting, and diarrhea were more common in the apremilast group (with 22, 9, and 12 incidents, respectively, among 55 patients) than in the placebo group (with 10, 1, and 2 incidents, respectively, among 56 patients), findings that were similar to those in previous studies of apremilast. There were two serious adverse events in patients receiving apremilast. CONCLUSIONS Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Behçets syndrome. This preliminary study was neither large enough nor long enough to assess long-term efficacy, the effect on other manifestations of Behçets syndrome, or the risk of uncommon serious adverse events. (Funded by Celgene; ClinicalTrials.gov number, NCT00866359.).

Amyloidosis and its related factors in Turkish patients with familial Mediterranean fever: a multicentre study

OBJECTIVE The primary aim of this study was to investigate the prevalence of amyloidosis and its related factors in a large number of FMF patients. METHODS Fifteen centres from the different geographical regions of Turkey were included in the study. Detailed demographic and medical data based on a structured questionnaire and medical records were collected. The diagnosis of amyloidosis was based on histological proof of congophilic fibrillar deposits in tissue biopsy specimens. RESULTS There were 2246 FMF patients. The male/female ratio was 0.87 (1049/1197). The mean age of the patients was 34.5 years (S.D. 11.9). Peritonitis was the most frequent clinical finding and it was present in 94.6% of patients. Genetic testing was available in 1719 patients (76.5%). The most frequently observed genotype was homozygous M694V mutation, which was present in 413 (24%) patients. Amyloidosis was present in 193 patients (8.6%). Male sex, arthritis, delay in diagnosis, M694V genotype, patients with end-stage renal disease (ESRD) and family history of amyloidosis and ESRD were significantly more prevalent in patients with amyloidosis compared with the amyloidosis-negative subjects. Patients with homozygous M694V mutations had a 6-fold higher risk of amyloidosis compared with the other genotypes (95% CI 4.29, 8.7, P < 0.001). CONCLUSION In this nationwide study we found that 8.6% of our FMF patients had amyloidosis and homozygosity for M694V was the most common mutation in these patients. The latter finding confirms the association of homozygous M694V mutation with amyloidosis in Turkish FMF patients.

A survey of phenotype II in familial Mediterranean fever

OBJECTIVE Phenotype II in familial Mediterranean fever (FMF) is the onset of amyloidosis before the onset of FMF with its typical attacks, or as an isolated finding in a member of an FMF family. Its presence was investigated by looking for proteinuria among the asymptomatic relatives of patients with FMF complicated by amyloidosis and among the asymptomatic relatives of patients with juvenile chronic arthritis (JCA) complicated by amyloidosis, used as controls. METHODS The relatives of the index patients (13 with FMF and amyloidosis) and controls (6 with JCA and amyloidosis) were screened for proteinuria. Rectal biopsies were performed when proteinuria was significant (⩾300 mg/d). RESULTS 461 relatives were screened in the FMF group and 269 among the controls. Two of the FMF relatives and one JCA relative had no symptoms of FMF but had significant proteinuria. Rectal biopsy for amyloidosis was negative in all instances of significant proteinuria. CONCLUSION Phenotype II is uncommon among the relatives of patients with FMF and amyloidosis.

Cytomegalovirus-induced interstitial pneumonitis in a patient with dermatomyositis

Dermatomyositis (DM) patients might present with pulmonary involvement as the first manifestation or during the follow-up period. It is sometimes difficult to determine whether the clinical manifestations related with pulmonary involvement are due to DM or to an infectious process. We report a case of DM patient who developed interstitial pneumonitis induced by cytomegalovirus (CMV) while receiving immunosuppressive treatment. To the best of our knowledge, this is the second report in the literature of interstitial pneumonitis secondary to CMV infection in a patient with DM.

Is anticoagulation unnecessary in Behcet's disease with deep venous thrombosis?

Dear Editor, I read with great interest the article by Kyong Ahn J et al. [1] entitled “Treatment of venous thrombosis associated with Behcet’s disease (BD): immunosuppressive therapy alone versus immunosuppressive therapy plus anticoagulation”. They reported that immunosuppressive therapy is essential, and anticoagulation therapy might not be required for the treatment of deep venous thrombosis (DVT) associated with BD. A few points warrant further explanation by the authors. Although the specific cause of vascular thrombosis seen in BD cases is not known as yet, endothelial cell injury and/ or pathological activation due to vasculitis is known to be a characteristic of BD [2]. In this setting, immunosuppressive treatment along with glucocorticoid is considered for the treatment of DVT in BD patients. However, inherited prothrombotic conditions, such as factor V Leiden mutation, prothrombin gene mutation, protein C, and S deficiency may result in the development of thrombosis as well [3–5]. Therefore, BD patients with DVT should be individualized according to the presence of inherited prothrombotic conditions. Authors compared the total levels of some anti-coagulation proteins like protein C, S, antithrombin III activity between treatment groups during the acute phase of thrombosis. As is well known, the levels of protein C, protein S, antithrombin III, anticardiolipin antibodies, and lupus antibodies may be low in the presence of acute thrombus. Therefore, to reach reliable conclusions, the levels of anticoagulant proteins and other prothrombotic conditions should have been evaluated after acute period subsided. It would be interesting to know whether the patients with recurrent thrombosis had factor V Leiden mutation and another inherited prothrombotic condition. My colleagues and I reported four BD patients with Budd–Chiari syndrome (BCS) associated with a history of previous DVT, three of whom had one or more inherited prothrombotic conditions [6]. One of the cases had three predisposing risk factors (Factor V Leiden mutation, protein C deficiency, and positive anticardiolipin antibodies) for thrombosis. He used warfarin for 4 years and continued his treatment with aspirin and colchicines after discontinuation of warfarin. However, he was observed to develop cerebral sagittal sinus thrombosis while on aspirin, and he was in remission for BD. The other BD patient with protein C deficiency had experienced a venous thrombosis before development of BCS, and he was using azathioprine and aspirin when BCS appeared. This observation led us to assume that long-term anticoagulation may be necessary for patients with BD who have inherited prothrombotic conditions, as well as for those with previous vascular thrombotic events. It is difficult to say without knowing anything on factor V Leiden mutation in the study groups. Authors concluded that increased levels of acute phase reactants during recurrence may reflect systemic inflammation secondary to BD. However, authors could not give us information about their patients’ clinical manifestations that will show clinical activation. Furthermore, CRP levels may increase in thrombotic events due to hypercoagulable conditions without inflammatory disease [7]. Therefore, increased CRP levels may be a secondary phenomenon to thrombotic process rather than BD. In conclusion, I believe that every BD patients with DVT should be evaluated whether there exist inherited Clin Rheumatol (2008) 27:405–406 DOI 10.1007/s10067-007-0805-9

Doppler sonography of ocular and carotid arteries in Behçet patients

To evalute by Doppler sonography carotid and ocular hemodynamics in Behçet disease with and without ocular involvement.

Low-dose natural human interferon-α lozenges in the treatment of Behçet's syndrome

OBJECTIVES There had been evidence that low-dose local IFN could be beneficial in the management of recurrent oral ulcers (OUs). We investigated the efficacy and collected initial data on the safety of low-dose natural human IFN-alpha administered by the oral mucosal route in Behçets syndrome (BS) in a placebo controlled, double blind study. METHODS Eighty-four (59 males and 25 females) patients with BS with mainly skin mucosa disease and a history of recurrent OU for > or = 1 year were studied. When they had at least two OUs with a total diameter of > or = 4 mm, they were randomly allocated to (i) 2000 IFN-alpha IU/day, (ii) 1000 IFN-alpha IU/day and (iii) placebo groups. Subjects were monitored weekly over an initial 4 weeks and bi-weekly for an additional 8 weeks of treatment. OU were counted and measured at each study visit. The primary efficacy end point was the difference in the total ulcer burden at Week 0 compared with that at Week 12. RESULTS Out of the 84 patients enrolled, 72 completed the trial. There were no statistically significant differences between the treatment arms in terms of the primary endpoint. CONCLUSIONS Low-dose natural human IFN-alpha did not have beneficial effects on reducing the total ulcer burden among BS patients from Turkey. The study also showed that counting the number of ulcers rather than measuring the size would be adequate in future studies. TRIAL REGISTRATION ClinicalTrials.gov, NCT00483184, http://www.clinicaltrials.gov/ct2/results?term=NCT00483184.

Retrospective evaluation of 22 patients with Takayasu’s arteritis

Takayasu’s arteritis (TA) is a rare, idiopathic, inflammatory, granulomatous vasculitis that affects the aorta and its primary branches. Clinical features and the pattern of arterial involvement show differences in different regions of the world according to ethnic influences. Our aim in this retrospective study was to evaluate the demographic, clinic, laboratory, and angiographic findings of 22 patients with TA followed by our clinic and also compare our results with series from the literature. The hospital files of the 22 patients followed by our clinic between 1998 and 2009 were retrospectively evaluated. We also compared our results with the series from the literature that we were able to reach by US National Library of Medicine, National Institute of Health. Gender distribution, age at diagnosis, and type of aortic involvement were similar with the study from Turkey. Different clinical manifestations of Takayasu’s arteritis have been described in different ethnic groups. We also want to underline the coincidence of TA and other rheumatic diseases such as sarcoidosis, SLE, RA, and psoriatic arthritis, different from other published series.

PTU-induced ANCA-positive vasculitis: an innocent or a life-threatening adverse effect?

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides are rare, but they can be triggered by chemicals, infections and drugs; among them, antithyroid drugs are common. Autoimmune disorders, such as vasculitis, are unusual, but serious complications of antithyroid therapy. Both propylthiouracil (PTU) and methimazole may induce ANCA-associated vasculitis. PTU-induced vasculitides may have different organ involvement patterns. Herein, we report four cases with ANCA-associated vasculitis with different clinical manifestations.